title: Gene expression profiles of ileal inflammatory bowel disease correlate with disease phenotype and advance understanding of its immunopathogenesis.
abstract: BACKGROUND
  Pouchitis may develop in patients with ulcerative colitis undergoing pouch surgery. We aimed to evaluate the de novo inflammation developing in the ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease (CD).
  
  
  METHODS
  Patients with ulcerative colitis pouch were prospectively recruited, stratified according to disease behavior into normal pouch, chronic pouchitis, and Crohn's-like disease of the pouch groups, and compared with controls. Gene expression analysis was performed using microarrays, validated by real-time polymerase chain reaction. Gene ontology and clustering were evaluated using bioinformatic tools.
  
  
  RESULTS
  Sixty-six subjects were recruited. Although in ulcerative colitis ileum there were no significant gene expression alterations, patients with normal pouch had 168 significant alterations (fold change ≥ 2, corrected P ≤ 0.05). In chronic pouchitis and Crohn's-like disease of the pouch, 490 and 1152 alterations were detected, respectively. High degree of overlap in gene expression alterations between the pouch subgroups was demonstrated. The magnitude of change correlated with pouch disease behavior. Gene expression profiles were more reflective of disease behavior compared with inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with pouchitis. Gene ontology analyses revealed multiple biological processes associated with pouch inflammation, including response to chemical stimulus, small molecule metabolic and immune system processes, and specific infection-related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis.
  
  
  CONCLUSIONS
  Gene alterations in pouch inflammation and CD overlap, suggesting that inflammatory bowel diseases is a spectrum, rather than distinct diseases. Pouchitis may serve as a model of CD. The novel pathways associated with inflammatory bowel diseases may decipher pathophysiology and suggest targets for intervention.
authors.affiliation: *Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; ‡IBD center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel; Departments of §Pathology, and ‖Surgery, Tel Aviv Medical Center, Tel Aviv, Israel; and ¶Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Shachar
authors.forename: Henit
authors.initials: H
authors.lastname: Yanai
authors.forename: Liran
authors.initials: L
authors.lastname: Baram
authors.forename: Hofit
authors.initials: H
authors.lastname: Elad
authors.forename: Elhanan
authors.initials: E
authors.lastname: Meirovithz
authors.forename: Amos
authors.initials: A
authors.lastname: Ofer
authors.forename: Eli
authors.initials: E
authors.lastname: Brazowski
authors.forename: Hagit
authors.initials: H
authors.lastname: Tulchinsky
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.forename: Iris
authors.initials: I
authors.lastname: Dotan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007079:Ileitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D019449:Pouchitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger